C-Reactive Protein in Stable Cystic Fibrosis: An Additional Indicator of Clinical Disease Activity and Risk of Future Pulmonary Exacerbations

Abstract

IntroductionIn stable adult cystic fibrosis (CF) patients, we assessed the role of baseline high sensitivity C-reactive protein (hs-CRP) on CF clinical variables and frequency of intravenous (IV) treated pulmonary exacerbations (PExs) 1-year post-baseline.MethodsWe recruited 51 clinically stable CF patients from our Adult CF Center. We incorporated collected parameters into Matouk CF clinical score and CF questionnaire-revised quality of life score (QOL). We used the clinical minus complications subscores as a clinical disease activity score (CDAS). We dichotomized our patients according to the cohort median baseline hs-CRP of 5.2 mg/L.ResultsPatients in the high hs-CRP group (≥ 5.2 mg/L) demonstrated worse CDAS (r=0.67, p=0.0001) and QOL scores (r=0.57, p=0.0017) at a given FEV1% predicted. In both hs-CRP groups, prior-year IV-treated PExs and baseline CDASs were significant predictors of future IV-treated PExs. Interestingly, the association between baseline CDAS and future PExs frequency was more robust in the high compared to the low hs-CRP group (r=−0.88, p<0.0001, r=−0.48, p=0.017, respectively) with a steeper regression slope (p=0.001). In addition, a significant interaction was demonstrated between elevated baseline hs-CRP levels and CDASs for the prediction of increased risk of future PExs (p=0.02). This interaction provided an additional indicator of clinical disease activity and added another dimension to the prior year PExs frequency phenotype to identify patients at increased risk for future PExs.ConclusionStable CF patients with elevated baseline hs-CRP (≥ 5.2 mg/L) demonstrated worse clinical disease activity and QOL scores at a given level of disease severity (FEV1% predicted). Elevated baseline hs-CRP values combined with clinical disease activity scores are associated with increased risk for future IV-treated PExs even in those with mild clinical disease activity scores.

Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

“…Moreover, absolute or delta CRP showed a smaller (and in case of deltas non-significant) correlation with FEV 1 than HE4. Interestingly, other authors had recently reported that variations of CRP levels could be used as an additional indicator of the overall severity of CF and that this biomarker could even predict pulmonary exacerbations [19]. While there was a strong correlation between HE4 and CRP levels in this study, our observation suggests that HE4 is a more suitable biomarker compared to CRP in this regard.…”

“…Currently, there are no unambiguous plasma/serum-based biomarkers for monitoring CFTR modulating therapy efficacy, thus, there is an unmet need to establish a sensitive and easily reproducible biomarker, which is easily performed and accessible, ideally plasma/ serum based. Several laboratory parameters have been investigated in this regard, especially for the prediction of pulmonary exacerbations, such as CRP and interleukin-1β levels in serum and soluble CD14 levels in plasma [19,27]. In addition, metalloproteinases 2 and 9, and IL-8 levels were analyzed in bronchoalveolar lavage samples [28].…”

“…CRP, as another inflammatory blood biomarker in CF [19], was measured in all cases. Of note, 26%, 17% and 22% of CRP values were undetectable (b0.5 mg/L) in cohorts 1-3, respectively.…”

Acute and Chronic Infection Management in CF

“…Calprotectin does demonstrate some early promise with some ability to predict PEx, but its clinical utility remains unclear [64]. Matouk et al showed that patients with a higher hsCRP were more likely to have more clinically active disease and future PEx [65]. Biomarker panels may prove to be more useful than any single biomarker.…”

C-reactive protein/albumin ratio is associated with lung function among children/adolescents with cystic fibrosis: a three-year longitudinal study

“…5 High levels of C-reactive protein are associated with lower forced expiratory volume in the first second in individuals with cystic fibrosis. 6 In addition to C-reactive protein levels, the C-reactive protein/albumin ratio can be evaluated and used as an inflammatory-nutritional factor. 7 The systemic inflammatory response is associated with a continuous catabolic response, which exerts an effect on fat-free mass and leads to reduced skeletal muscle mass and wastage of inspiratory muscles.…”